General Information:

Id: 448
Diseases: Parkinson disease
Drosophila melanogaster
BTO:0000142 brain
article
Reference: Imai Y et al.(2008) Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila EMBO J. 27: 2432-2443 [PMID: 18701920]

Interaction Information:

Comment dLRRK regulates dopaminergic neuron function and maintenance. In animals expressing dLRRK mutants, known to be pathogenic in human, a significant reduction of DA neurons has been observed.
Formal Description
Interaction-ID: 1981

gene/protein

LRRK2

affects_activity of

process

neuron death

Comment dLRRK regulates dopaminergic neuron function and maintenance. In animals expressing dLRRK mutants, known to be pathogenic in human, a significant reduction of DA neurons has been observed.
Formal Description
Interaction-ID: 1986

gene/protein mutant

LRRK2-mut

increases_activity of

process

neuron death

Comment Flies expressing LRRK-mutants showed significantly higher sensitivity to exogenous ROS inducers paraquat and H(2)O(2).
Formal Description
Interaction-ID: 1987

gene/protein mutant

LRRK2-mut

increases_activity of

Comment Flies expressing LRRK-mutants showed significantly higher sensitivity to exogenous ROS inducers paraquat and H(2)O(2).
Formal Description
Interaction-ID: 1989

gene/protein mutant

LRRK2-mut

increases_activity of

drug/chemical compound

Paraquat

Comment dLRRK phosphorylates 4E-BP, but did not phosphorylate eIF4E, the binding partner of 4E-BP.
Formal Description
Interaction-ID: 1992

gene/protein

LRRK2

increases_phosphorylation of

gene/protein

EIF4EBP1

Comment dLRRK phosphorylates 4E-BP, but did not phosphorylate eIF4E, the binding partner of 4E-BP.
Formal Description
Interaction-ID: 1999

gene/protein

LRRK2

NOT affects_phosphorylation of

gene/protein

EIF4E

Drugbank entries Show/Hide entries for EIF4E
Comment 4E-BP is a negative regulator of eIF4E-mediated protein translation.
Formal Description
Interaction-ID: 2000

gene/protein

EIF4EBP1

decreases_activity of

gene/protein

EIF4E

Drugbank entries Show/Hide entries for EIF4E
Comment Blockage of 4E-BP phosphorylation and the consequent tighter binding and stronger inhibition of eIF4E lead to higher stress response. Overexpression of eIF4E significantly sensitizied animals to oxidative stress response, similar to the effect induced by mutant dLRRK overexpression.
Formal Description
Interaction-ID: 2002

gene/protein

EIF4EBP1

affects_activity of

Comment dLRRK2-mut stimulates eIF4E-mediated protein translation indirectly by increasing phosphorylation of 4E-BP resulting in a weaker binding of 4E-BP to eIF4E.
Formal Description
Interaction-ID: 2098

gene/protein mutant

LRRK2-mut

increases_activity of

gene/protein

EIF4E

indirectly by increasing phosphorylation of 4E-BP
Drugbank entries Show/Hide entries for EIF4E
Comment LRRK mutants phosphorylates 4E-BP resulting in weaker binding of 4E-BP to eIF4E.
Formal Description
Interaction-ID: 2104

gene/protein mutant

LRRK2-mut

decreases_activity of

gene/protein

EIF4EBP1

Comment Flies expressing LRRK-mutants showed significantly higher sensitivity to exogenous ROS inducers paraquat and H(2)O(2).
Formal Description
Interaction-ID: 3813

gene/protein mutant

LRRK2-mut

increases_activity of

drug/chemical compound

H2O2